Novel aryl c-xyloside compounds, and cosmetic use

ABSTRACT

The present invention relates to novel compounds of formula (I) 
     
       
         
         
             
             
         
       
     
     where:
     X is an —OH or ═O grouping;   n is an integer between 0 and 5;   R′ is H or a C 1 -C 4  alkyl radical,   when n≧2, two adjacent —OR′ groupings can together form the divalent radical —O—CH 2 —O—;   except when X═OH, the compound does not comprise a double ethylene link in the alpha position of the carbon having said OH.   

     The invention also relates to the salts thereof, to the optical isomers thereof, to the cosmetic and pharmaceutical compositions containing same, and to the use thereof to prevent and cosmetically treat the signs of aging on the skin.

The present invention relates to novel aryl C-xyloside derivatives, tothe compositions, in particular cosmetic compositions, comprising thesame, and also to the use thereof for combating skin aging.

Women and men currently have a tendency to wish to appear youthful foras long as possible and consequently seek to soften the signs of agingon the skin, which are reflected in particular by wrinkles and finelines. In this respect, the media and the fashion world report aboutproducts intended to keep the skin radiant and wrinkle-free for as longas possible, which are signs of youthful skin, and all the more so sincethe physical appearance acts on the psyche and/or on the morale.

Up until now, wrinkles and fine lines were treated using cosmeticproducts containing active agents acting on the skin, for example byimproving its cell renewal or alternatively by promoting the synthesis,or preventing the degradation, of the elastic fibers which make up theskin tissue.

It is known that human skin consists of two tissues, a surface tissue,the epidermis, and a deep tissue, the dermis.

Natural human epidermis is composed mainly of three types of cells:keratinocytes, which form the vast majority, melanocytes and Langerhanscells. Each of these cell types contributes, by virtue if its ownfunctions, to the essential role played in the body by the skin, inparticular the role of protecting the body against external attacks(climate, ultraviolet rays, tobacco, etc.), known as the “barrierfunction”.

The dermis provides the epidermis with a solid support. It is also itsfeeder element. It consists mainly of fibroblasts and an extracellularmatrix composed predominantly of collagen, elastin and a substance knownas ground substance. These components are synthesized by thefibroblasts. Leucocytes, mast cells or else tissue macrophages are alsofound therein. Finally, blood vessels and nerve fibers pass through thedermis.

The extracellular matrix of the dermis is composed of proteins belongingto several major families: collagens, matrix glycoproteins other thancollagens (fibronectin, laminin), elastin and proteoglycans.Glycosaminoglycans in free form (i.e. not bound to a protein) are alsofound in the extracellular matrix of the dermis.

It is now well established that specific interactions exist betweenthese various classes of proteins so as to give rise to a functionaltissue.

An extracellular space (micromatrix) also exists in the epidermis. Thisspace plays an extremely important functional role in cell tissuerenewal and/or maintenance.

Proteoglycans are complex macromolecules consisting of a branchedcentral protein trunk, or protein network, to which a very large numberof polysaccharide side chains known as glycosaminoglycans are attached.

In the remainder of the present application, the abbreviation PGs willbe used to denote proteoglycans and the abbreviation GAGs will be usedto denote glycosaminoglycans.

GAGs were for a long time referred to as acidic mucopolysaccharidesowing to their high water-retaining capacity, their carbohydrate natureand their acidic nature originating from their multiple negativecharges.

Thus, the polarity of GAGs makes them implicitly participate in certainbiological functions such as tissue hydration, cation binding or anionic filtration barrier role.

PGs and GAGs are synthesized by various cells in the dermis and theepidermis: fibroblasts, keratinocytes and melanocytes.

Fibroblasts synthesize predominantly collagens, matrix glycoproteinsother than collagens (fibronectin, laminin), GAGs, proteoglycans andelastin. Keratinocytes synthesize predominantly sulfated GAGs andhyaluronic acid, while melanocytes do not apparently produce hyaluronicacid.

At the time of their incorporation into a PG, GAGs in the form of linearchains composed of repeats of a base disaccharide always containing ahexosamine (glucosamine or galactosamine) and another monosaccharide(glucuronic acid, iduronic acid or galactose). The glucosamine is eitherN-sulfated or N-acetylated. On the other hand, the galactosamine isalways N-acetylated. In addition, there may be sulfate groups O-linkedto the hexosamine, uronic acid and galactose.

The strong anionic nature of GAGs is explained by the presence ofcarboxylate groups within the hexuronic acids (glucuronic acid andiduronic acid) and of O- and N-linked sulfate groups.

The main GAGs are hyaluronic acid or hyaluronan (HA), heparan sulfate(HS), heparin (HP), chondroitin, chondroitin sulfate (CS), chondroitin4-sulfate or chondroitin sulfate A (CSA), chondroitin 6-sulfate orchondroitin sulfate C (CSC), dermatan sulfate or chondroitin sulfate B(CSB) and keratan sulfate (KS), which differs from the otherglycosaminoglycans by the presence of galactose in place of uronic acid.

Proteoglycans (PGs) are formed by the anchoring of several GAG chains ona polypeptide chain (referred to as carrier protein or core protein).

GAGs can also exist in the extracellular matrix in free form, i.e. notbound to a matrix protein: this is in particular the case of hyaluronicacid.

When PGs are synthesized, the GAGs are polymerized from these anchoringstructures.

The synthesis of GAGs requires the coordinated and concerted action ofvery specific enzymes (transferases, epimerases, sulfotransferases)which are adjacent in the membrane of the endoplasmic reticulum and ofthe golgi apparatus. A multitude of biochemical reactions(N-deacetylation, N- and O-sulfations, epimerization) then modify thetwo constituent monosaccharides of the base unit in a nonuniform manneralong the chain. From one heparan sulfate chain to the other, forexample, the glucuronic acid/iduronic acid ratio, the nature, the numberand the position of the O-sulfations, and also the N-sulfate/O-sulfateratio can vary, which potentially offers an immense structuraldiversity.

In general, the biological roles of PGs are very diversified, rangingfrom a passive function of mechanical support (for example serglycins)or a molecular filtration ionic barrier role (for example, perlecan andbamacan of the glomerular basal membrane), to more specific effects incell adhesion, spreading, proliferation and differentiation ormorphogenesis, or to highly specific effects of PG-protein interactions,such as the betaglycan receptor function or the interaction of decorinwith collagen. They also play a fundamental role in the controlledrelease of various growth factors.

One of the roles of dermal connective tissue is to protect the bodyagainst external attacks while simultaneously forming an informativeinterface.

To do this, the dermis has high mechanical strength while maintaining,however, great flexibility.

Its strength is provided by the dense network of collagen fibers, but itis the PGs and the hyaluronic acid which, by providing themoisturization, distribution and flexibility of the fibers, make thedifference between the skin and, for example, leather.

The PGs constitute 0.5% to 2% of the dry weight of the dermis, collagenalone representing up to 80% thereof.

The concentration and distribution in human skin of GAGs and PGs varywith age.

Hyaluronic acid or hyaluronan (HA) is the main GAG of the dermis, thelatter containing half the HA of the body.

The synthesis of HA is performed in particular by the fibroblasts, closeto the inner face of the plasma membrane. It is performed continuously.This gigantic polysaccharide (several million daltons) has a very highintrinsic viscosity, ensuring the moisturization and assembly of thevarious components of the connective tissue by forming supramolecularcomplexes.

Dermatan sulfate (DS), which is first isolated in the dermis, is alsovery abundant in the skin. It constitutes 40% to 50% of the dermal GAGs.

In parallel with the mechanisms contributing to the development of thesespecialized extracellular matrices, continuous remodeling processesexist, the regulation of which depends on the balance between synthesisand degradation of the protein components of the matrix.

Several families of matrix proteases are now described, as are thefactors involved in their activation-inactivation.

During chronological and/or photoinduced aging, the dermis and theepidermis undergo numerous modifications and degradations which arereflected, with age, by flaccidness and a loss of suppleness of theskin.

Among the components degraded (in particular collagen and elastin), thePGs and GAGs are also adversely affected. Specifically, during aging,the fibroblasts and the keratinocytes produce less and less PGs and GAGsand their synthesis is imperfect. This results in considerabledisorganization: the deposition of GAGs on the protein backbone formingthe PG is abnormal, the consequence of this being reduced avidity ofthese PGs for water and therefore a reduction in the moisturization andtonicity of tissues.

Restoring a normal production of PGs and GAGs by fibroblasts andkeratinocytes contributes partially toward compensating for the loss ofmoisturization of the skin.

The degradation of these matrices thus contributes to the phenomenon ofdryness and loss of suppleness of the skin.

The importance of having available products of which the effects aredirected toward maintaining the level of PGs and GAGs in the skin andthus of maintaining, inter alia, good moisturization and good supplenessof the skin, can thus be appreciated.

It is known from document WO 02/051828 to use C-glycoside compounds forincreasing the synthesis of glycosaminoglycans by fibroblasts and/orkeratinocytes.

Other C-glycoside compounds for depigmenting the skin are also knownfrom document WO 2006/128738.

The applicant has discovered, surprisingly and unexpectedly, that otheraryl C-glycoside derivatives are capable of improving the synthesis ofsulfated glycosaminoglycans such as chondroitin sulfate and dermatansulfate.

Their effectiveness is greater than that of the C-glycoside compoundsalready known. They are more effective for improving epidermal renewaland firmness of the skin and for more effectively combating the signs ofaging of the skin. They also have a beneficial effect on the structureof the dermal-epidermal junction, in particular on the cohesion betweendermis and epidermis.

These novel compounds therefore find a particular application incosmetic or pharmaceutical compositions, in particular dermatologicalcompositions, intended for preventing and/or cosmetically treating agingof the skin; especially preventing and/or treating, in particulartopically, the signs of aging on the skin, and most particularly thesigns on the skin related to wrinkled skin, skin exhibiting adetrimental modification of its viscoelastic or biomechanicalproperties, skin exhibiting a detrimental modification in the cohesionof its tissues, thinned skin and/or skin exhibiting a detrimentalmodification of its surface appearance.

The compositions according to the invention can make it possible moreparticularly to maintain and/or restore the stretchability, tonicity,firmness, suppleness, density and/or elasticity properties of the skin.

The expression “biomechanical properties of the skin” is herein intendedto mean the stretchability, tonicity, firmness, suppleness and/orelasticity properties of the skin.

The expression “signs of aging on the skin” is herein intended to meanany modification of the external appearance of the skin due to agingwhich is either chronobiological and/or extrinsic, in particularphotoinduced or hormonal; among these signs, it is possible todistinguish:

-   -   wrinkled skin, which is reflected in particular by the        appearance of wrinkles and/or fine lines,    -   skin exhibiting a detrimental modification of its viscoelastic        or biomechanical properties, or skin exhibiting a lack of        elasticity and/or of stretchability and/or of firmness and/or of        suppleness and/or of tonicity, which is reflected in particular        by wizened, flaccid or slack skin or skin that has sagged,    -   skin exhibiting a detrimental modification of the cohesion of        its tissues,    -   thinned skin,    -   skin exhibiting a detrimental modification of its surface        appearance, which is in particular reflected by a detrimental        modification of the grain of the skin, for example a roughness.

A subject of the present invention is therefore novel amino C-glycosidecompounds of formula (I) as defined hereinafter.

The invention also relates to a cosmetic or pharmaceutical compositioncomprising at least one such compound in a physiologically acceptablemedium.

The compounds according to the invention therefore correspond to formula(I) below:

in which:X denotes an —OH or ═O group;n is an integer ranging from 0 to 5;R′ denotes:a hydrogen atom ora linear C₁-C₄ or branched C₃-C₄ alkyl radical, or an unsaturated C₃-C₄hydrocarbon-based radical,when n≧2, two adjacent —OR′ groups can together form the divalentradical —O—CH₂—O—;with the proviso that, when X═OH, the compound does not comprise anethylenic double bond in the alpha-position of the carbon bearing thisOH; and also the salts thereof, and the optical isomers thereof.

In the context of the present invention, the term “alkyl” means asaturated or unsaturated hydrocarbon-based chain. Among the alkyl groupssuitable for implementation of the invention, mention may in particularbe made of methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl,isobutyl, sec-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decylgroups.

Preferably,

X denotes an —OH or ═O group;n is an integer ranging from 0 to 3;R′ denotes:a hydrogen atom ora linear C₁-C₄ alkyl radical, in particular a methyl or n-butyl radical;or a —CO—CH₃ radical;when n≧2, two adjacent —OR′ groups can together form the divalentradical —O—CH₂—O—.

Preferentially:

X denotes an —OH or ═O group;n is an integer ranging from 0 to 3;R′ denotes:a hydrogen atom ora methyl radical.

In particular, n and R′ may be such that the aromatic part

of the compounds of formula (I°) can correspond to one of the followingstructures:

Mention may in particular be made of the following compounds of formula(I) (including the salts thereof or the solvates thereof):

-   1-(α,β)-D-xyopyranosyl-4-(4-hydroxy-3-methoxyphenyl)butan-2-ol    (compound 1):

-   1-(α,β)-D-xylopyranosyl-4-(4-hydroxy-methoxyphenyl)butan-2-one    (compound 2):

-   1-(α,β)-D-xylopyranosyl-4-(4-hydroxyphenyl)butan-2-ol (compound 3):

-   1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-one (compound 4):

-   (3E)-1-(α,β)-D-xyopyranosyl-4-phenylbut-3-en-2-one (compound 5):

-   (3E)-1-(α,β)-D-xylopyranosyl-4-[4-hydroxy-(3,5)-dimethoxyphenyl]but-3-en-2-one    (compound 6):

-   1-(α,β)-D-xylopyranosyl-4-[(3,4)-methylenedioxypheny]butan-2-ol    (compound 7):

-   1-(α,β)-D-xylopyranosyl-4-(2-hydroxyphenyl)butan-2-ol (compound 8):

-   1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-ol (compound 9):

The acceptable solvates of the compounds described in the presentinvention comprise conventional solvates such as those formed during thelast step of preparation of said compounds owing to the presence ofsolvents. By way of example, mention may be made of the solvates owingto the presence of water or of linear or branched alcohols such asethanol or isopropanol.

The compounds of formula (I) can be prepared according to scheme Ihereinafter:

by reacting the C-β-D-xylopyranoside-n-propan-2-one (A) (compounddescribed in example 1 of application WO 02/051828) with 1 to 2equivalents of benzaldehyde of formula (III) (Ald) in which n and R′have the meanings as described above in the compounds of formula (I), inparticular at ambient temperature (25° C.), in a polar solvent, such aswater, ethanol, isopropanol or methanol, in the presence of a base (forexample, sodium hydroxide or sodium methoxide), in particular for 1 to20 hours.

The aldolization product (B) obtained can then be partially reduced in aknown manner by catalytic hydrogenation (for example Pd/C/H₂) so as toobtain the compound (C). The compound (C) can in turn be continuouslyreduced by means of a hydride (for example sodium borohydride) or elseby catalytic hydrogenation with palladium-on-carbon, followed by a stepof hydrogenation in the presence of hydrogen under pressure, so as toobtain the compound (D). The compounds B, C and D are compounds inaccordance with the structure of formula (I) described above.

The present invention also relates to a composition comprising, in aphysiologically acceptable medium, a compound of formula (I) asdescribed above. The composition is in particular a cosmetic ordermatological composition.

The compound of formula (I) may be present in the cosmetic orpharmaceutical compositions in an amount which can be between 0.01% and10% by weight, preferably between 0.1% and 5% by weight, and inparticular between 0.5% and 3% by weight, relative to the total weightof the composition.

The composition also comprises a physiologically acceptable medium,which will preferentially be a cosmetically or pharmaceutically, inparticular dermatologically, acceptable medium, i.e. a medium which hasno unpleasant odor, color or appearance, and which does not cause anytingling, tautness or redness unacceptable to the user. In particular,the composition is suitable for topical application to the skin.

The term “physiologically acceptable medium” is understood to mean amedium which is compatible with the keratin materials of human beings,such as bodily or facial skin, the lips, the mucous membranes, theeyelashes, the nails, the scalp and/or the hair.

The composition according to the invention may also comprise any of thecosmetic adjuvants normally used in the field of application envisioned.

Mention may in particular be made of water, organic solvents, inparticular C₁-C₆ alcohols and C₂-C₁₀ carboxylic acid esters;hydrocarbon-based oils, silicone oils, fluoro oils, waxes, pigments,fillers, dyes, surfactants, emulsifiers, cosmetic or dermatologicalactive agents, UV-screening agents, film-forming polymers, hydrophilicor lipophilic gelling agents, thickeners, preservatives, fragrances,bactericides, odor absorbers and antioxidants.

These optional adjuvants may be present in the composition in aproportion of from 0.001% to 80% by weight, in particular 0.1% to 40% byweight, relative to the total weight of the composition.

Depending on their nature, these adjuvants may be introduced into thefatty phase or into the aqueous phase of the composition, or into lipidvesicles. In any event, these adjuvants, and also the proportionsthereof, will be chosen by those skilled in the art in such a way thatthe advantageous properties of the compounds according to the inventionare not, or not substantially, impaired by the addition envisioned.

As oils that can be used in the invention, mention may be made ofmineral oils (liquid petroleum jelly), oils of plant origin (avocadooil, soya oil), oils of animal origin (lanolin), synthetic oils(perhydrosqualene), silicone oils (cyclomethicone) and fluoro oils(perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids andwaxes (carnauba wax, ozokerite) can also be used as fats.

As hydrophilic gelling agents or thickeners, mention may be made ofcarboxyvinyl polymers (carbomer), acrylic copolymers, such asacrylate/alkyl acrylate copolymers, polyacrylamides, polysaccharides,natural gums and clays; as lipophilic gelling agents or thickeners,mention may be made of modified clays such as bentones, metal salts offatty acids, and hydrophobic silica.

As active agents, it will be advantageous to introduce into thecomposition used according to the invention at least one compound chosenfrom: desquamating agents; moisturizing agents; depigmenting orpropigmenting agents; anti-glycation agents; NO-synthase inhibitors;agents which stimulate the synthesis of dermal or epidermalmacromolecules and/or prevent degradation thereof; agents whichstimulate fibroblast and/or keratinocyte proliferation or stimulatekeratinocyte differentiation; muscle relaxants and/ordermo-decontracting agents; tensioning agents; anti-pollution agentsand/or free-radical scavengers; agents which act on themicrocirculation; agents which act on the energy metabolism of cells;and mixtures thereof.

Examples of such additional compounds are: retinol and derivativesthereof, such as retinyl palmitate; ascorbic acid and derivativesthereof, such as magnesium ascorbyl phosphate and ascorbyl glucoside;tocopherol and derivatives thereof, such as tocopheryl acetate;nicotinic acid and precursors thereof, such as nicotinamide; ubiquinone;glutathione and precursors thereof, such asL-2-oxothiazolidine-4-carboxylic acid; plant extracts, and in particularplant proteins and hydrolysates thereof, and also phytohormones; marineextracts, such as algal extracts; bacterial extracts; sapogenins such asdiosgenin and extracts of Wild Yam containing the same; ceramides;hydroxy acids, such as salicylic acid and 5-n-octanoylsalicylic acid;resveratrol; oligopeptides and pseudodipeptides and acylated derivativesthereof; manganese salts and magnesium salts, in particular gluconates;and mixtures thereof.

As indicated above, the composition according to the invention may alsocontain UV-screening agents or photoprotective agents which are activein the UVA and/or UVB range, in the form of organic or inorganiccompounds, the latter being optionally coated so as to make themhydrophobic.

The organic photoprotective agents may in particular be chosen from:anthranilates, in particular menthyl anthranilate; benzophenones, inparticular benzophenone-1, benzophenone-3, benzophenone-5,benzophenone-6, benzophenone-8, benzophenone-9, la benzophenone-12, andpreferentially benzophenone-3 (oxybenzone), or benzophenone-4 (UvinulMS40 from BASF); benzylidenecamphors, in particular3-benzylidenecamphor, benzylidenecamphorsulfonic acid, camphorbenzalkonium methosulfate, polyacrylamidomethylbenzylidenecamphor,terephthalylidenedicamphorsulfonic acid, and preferentially4-methylbenzylidenecamphor (Eusolex 6300 from Merck); benzimidazoles, inparticular benzimidazilate (Neo Heliopan AP from Haarmann and Reimer),or phenylbenzimidazolesulfonic acid (Eusolex 232 from Merck);benzotriazoles, in particular drometrizole trisiloxane, ormethylene[bis(benzotriazolyl)tetramethylbutyl]phenol (Tinosorb M fromCiba); cinnamates, in particular cinoxate, DEA methoxycinnamate,diisopropyl methylcinnamate, glycerylethylhexanoate dimethoxycinnamate,isopropyl methoxycinnamate, isoamyl cinnamate, and preferentiallyethocrylene (Uvinul N35 from BASF), octyl methoxycinnamate (Parsol MCXfrom Hoffmann La Roche), or octocrylene (Uvinul 539 from BASF);dibenzoylmethanes, in particular butyl methoxydibenzoylmethane (Parsol1789); imidazolines, in particular ethylhexyl dimethoxybenzylidenedioxoimidazoline; PABAs, in particular ethyldihydroxypropyl PABA,ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-25 PABA, andpreferentially diethylhexylbutamidotriazone (Uvasorb HEB from 3V Sigma),ethylhexyltriazone (Uvinul T150 from BASF), or ethyl PABA (benzocaine);salicylates, in particular dipropylene glycol salicylate, ethylhexylsalicylate, homosalate, or TEA salicylate; triazines, in particularanisotriazine (Tinosorb S from Ciba); drometrizole trisiloxane.

The inorganic photoprotective agents preferably consist of zinc oxideand/or titanium dioxide, preferably of nanometric size, optionallycoated with alumina and/or with stearic acid.

This composition may be in any of the galenical forms normally used inthe cosmetics or pharmaceutical field, and in particular in the form ofan aqueous or aqueous-alcoholic, optionally gelled, solution, of adispersion of the lotion type, which is optionally two-phase, of anemulsion obtained by dispersion of a fatty phase in an aqueous phase(O/W) or vice versa (W/O), or a triple emulsion (W/O/W or O/W/O) or of avesicular dispersion of ionic and/or nonionic type, or of an aqueous oroily gel. These compositions are prepared according to the usualmethods. A composition in the form of an emulsion, in particular anoil-in-water emulsion, is preferably used according to this invention.

The composition may be more or less fluid and may have the appearance ofa white or colored cream, an ointment, a milk, a lotion, a serum, apaste, a gel or a foam. It may optionally be applied in the form of anaerosol. It may also be in solid form, in particular in the form of astick.

When the composition is an emulsion, the proportion of the fatty phasemay range from 5% to 80% by weight, preferably from 8% to 50% by weight,relative to the total weight of the composition. The emulsifier and thecoemulsifier may be present in a proportion ranging from 0.3% to 30% byweight, and preferably from 0.5% to 20% by weight, relative to the totalweight of the composition.

The composition according to the invention may constitute a skincarecomposition, in particular a cleansing, protection, treatment, or carecream for the face, for the hands, for the feet, for the majoranatomical folds or for the body (for example, day creams, night creams,makeup-removing creams, foundation creams, antisun creams); amakeup-removing milk, a protective or care body milk, an antisun milk; alotion, a gel or foam for skincare, such as a cleansing lotion.

The composition according to the invention is advantageously ananti-aging, in particular care, composition intended for treating and/orcombating, cosmetically, the external signs of aging of the skin; thecomposition is more particularly a care composition for mature skin.

The composition may also be a makeup composition, in particular afoundation.

The invention also relates to a method for cosmetic treatment of theskin, comprising the application, to the skin, of a cosmetic compositionas defined above. This method finds an advantageous application intreatment of the skin, in particular of mature skin and/or wrinkledskin, in particular of the face, especially of the forehead, the neckand/or the hands.

The invention also relates to the nontherapeutic cosmetic use of acosmetic composition as defined above or of a compound of formula (I) asdescribed above, for preventing and/or treating the signs of aging onthe skin, in particular the signs of the skin chosen from wrinkled skin,skin exhibiting a detrimental modification of its viscoelastic orbiomechanical properties, skin exhibiting a detrimental modification inthe cohesion of its tissues, thinned skin, and skin exhibiting adetrimental modification of its surface appearance.

The invention also relates to the nontherapeutic cosmetic use of acomposition as defined above or of a compound of formula (I) asdescribed above, for improving the firmness of the skin and/or forimproving the structure of the dermal-epidermal junction and/or forreinforcing the cohesion between the dermis and the epidermis.

The invention is illustrated in greater detail by the followingnonlimiting examples.

EXAMPLE 1 Synthesis of1-(α,β)-D-xylopyranosyl-4-(4(4-hydroxy-3-methoxy-phenyl)butan-2-one(Compound 2)

In 50 ml of anhydrous methanol, 5 g (1 eq) ofC-β-D-xylopyranoside-n-propan-2-one were reacted with sodium methoxideat 30% in methanol (7.55 ml, 1.5 eq), and then 6.69 g (1.05 eq) of4-benzyloxy-3-methoxybenzaldehyde were added.

The reaction medium was stirred for 15 hours at ambient temperature (25°C.), and was then diluted in dichloromethane and then washed with anaqueous solution of NH₄Cl. The organic phase was then dried over sodiumsulfate and then concentrated under vacuum. The light brown oil obtainedwas purified on silica gel so as to obtain the correspondingintermediate (B) (pale yellow solid, yield of 30%).

The reaction intermediate (B) obtained (2 g, 1 eq) was solubilized in awater/ethanol mixture (5 ml/50 ml). Palladium-on-carbon at 10% (400 mg,0.78 equivalent) was then added, as was cyclohexene (10 ml, 20.5equivalents). The reaction medium was brought to reflux for 5 hours, andthen left to cool to ambient temperature so as to be filtered andconcentrated under vacuum. 1.57 g (1.57 g, slightly greenish-yellow oil)corresponding to compound 2 were thus obtained.

The ¹H NMR, ¹³C NMR and mass spectra are in accordance with thestructure of the expected product.

EXAMPLE 2 Synthesis of1-(α,β)-D-xylopyranosyl-4-(4-hydroxy-3-methoxy-phenyl)butan-2-ol

The compound 2 obtained in example 1 (1.57 g, 1 eq) was solubilized inethanol (20 ml) and then sodium borohydride (0.182 g, 1 eq) was added insmall portions. The medium was stirred at ambient temperature for 12hours. Acetone was then added in order to destroy the excess sodiumborohydride, followed by aqueous hydrochloric acid (1N) in order toadjust the pH to 2. The reaction medium was then concentrated undervacuum, and the resulting product was taken up in water and then washedtwice with ethyl acetate. The aqueous phase was then extracted withbutanol, and the organic phases were combined and concentrated undervacuum. The crude product obtained was purified on silica gel, so as toobtain 0.53 g (yield of 34%) of a slightly yellow oil corresponding tothe pure compound 1.

The ¹H NMR. ¹³C NMR and mass spectra are in accordance with thestructure of the expected product.

EXAMPLE 3 Synthesis of(3E)-1-(α,β)-D-xylopyranosyl-4-phenylbut-3-en-2-one

In 50 ml of ethanol, 2 g (10.5 mmol) ofC-β-D-xylopyranoside-n-propan-2-one were reacted with 1.2 g (11.6 mmol)of benzaldehyde, and then 5.8 ml (15.8 mmol) of a solution of sodiummethoxide at 21% in ethanol were added. The medium was stirred for onehour and then the reaction was stopped by adding a saturated solution ofammonium chloride.

The reaction medium was then concentrated under vacuum and taken up inwater. The aqueous phase was extracted with butanol. The organic phaseswere dried and concentrated under vacuum. The crude product obtained waspurified on silica gel, so as to obtain 700 mg (yield 25%) of the pureexpected product in the form of a white solid.

The ¹H NMR, ¹³C NMR and mass spectra are in accordance with thestructure of the expected product.

EXAMPLE 4 Synthesis of 1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-one

In a round-bottomed flask provided with a magnetic stirrer, 12 g of thecompound 5 of example 3 were introduced into 70 ml of methanol, and 0.5g of palladium-on-carbon at 10 mol % was added. The reaction mixture wasstirred and placed under hydrogen pressure (100 000 Pa, i.e. 1 bar) for15 hours. Next, the insoluble material was filtered off through a layerof celite, and the filtrate was evaporated under vacuum. 12 g (yield99%) of compound 4 were obtained in the form of an off-white solidproduct.

EXAMPLE 5 Synthesis of: (compound 4):1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-ol

In a 250 ml round-bottomed flask, provided with a magnetic stirrer, 12 g(0.043 mol) of the compound 4 of example 4 were introduced, undernitrogen, into 100 ml of methanol. 1.954 g (0.0514 mol, 1.2 eq.) ofsodium borohydride were then added in small portions with vigorousstirring at −20° C. At the end of the addition, the stirring wasmaintained for 10 minutes at 0° C., and then the mixture was hydrolyzedat this temperature, by means of HCl (3N) up to pH=4. The reactionmixture was then evaporated to dryness under vacuum. The residueobtained was diluted with acetone, and then filtered so as to remove thesalts formed, and the filtrate was evaporated and then dried undervacuum. The crude product obtained was purified by flash chromatographyon a silica column (eluent: ether, then acetone), so as to recover theexpected compound 9 (yield 72%) in the form of off-white crystals.

EXAMPLE 6 Synthesis of1-(α,β)-D-xylopyranosyl-4-(2-hydroxyphenyl)-butan-2-ol

a) Synthesis of Compound A of Formula

C-β-D-Xylopyranoside-n-propan-2-one (1 equiv., 4.00 g) in solution in anethanol (4.5 ml)+water (3.5 ml) mixture was treated with an aqueoussolution of sodium hydroxide (3.5 equiv., 2.94 g, in 27 ml of water) atambient temperature. After 2 hours of stirring, salicylaldehyde (1.2equiv., 2.7 ml) was added dropwise at ambient temperature. After 20hours of stirring, the pH was adjusted to 6 and then the reactionmixture was concentrated. The TLC analysis of the reaction cruderevealed the formation of a largely predominant new product (Rf=0.38 forCH₂Cl₂/MeOH: 80/20)

Purification of this residue by silica column chromatography (soliddeposit, CH₂Cl₂/MeOH: 80/20) makes it possible to recover the expectedcompound A in the form of an orange powder (4.27 g, yield=69%).

b) Synthesis of Compound B of Formula

Compound A (1 equiv., 4.2 g) was dissolved in methanol (150 ml) and wasthen treated with NaBH₄ (2 equiv., 1.1 g), which was added at ambienttemperature, portionwise, in order to limit the effervescence whichoccurs. The reaction mixture was stirred for 3 hours, after which time aTLC analysis of the reaction mixture revealed that the starting producthad completely disappeared. The excess reducing agent was neutralized byadding a saturated aqueous solution of ammonium chloride (20 ml), andthen the reaction mixture was concentrated. The reaction crude waspurified by silica column chromatography (Rf=0.45 for CH₂Cl₂/MeOH:80/20), so as to obtain compound B.

c) Synthesis of 1-(α,β)-D-xylopyranosyl-4-(2-hydroxyphenyl)butan-2-ol

Compound B (120 mg) was dissolved in 10 ml of ethanol, to which 3 dropsof water were added, and was then hydrogenated at 30° C. using 10% Pd/Ccatalyst. After evaporation, the expected product is obtained in theform of a beige oil (60 mg, yield=49%).

EXAMPLE 7

Study of the effect of C-glycoside derivatives on sulfatedglycosaminoglycan synthesis on fibroblasts and on keratinocytes:

The study is carried out by measuring the incorporation of radioactiveglucosamine into the matrix neosynthesized by cultures of normal humandermal fibroblasts or by keratinocytes. The incorporation of radioactiveglucosamine indicates specific neosynthesis of glycosaminoglycans via anincorporation of the acetylated form of this glucosamine.

The fibroblast cultures are performed according to conventional cellculture methods, namely in DMEM medium sold by the company Gibco, in thepresence of L-glutamine (2 mM), of penicillin (50 IU/ml) and of 10% offetal calf serum (Gibco).

The keratinocyte cultures are performed in keratinocyte-SFM medium soldby the company Gibco, in the presence of EGF (Epidermal Growth Factor)(0.25 ng/ml), of pituitary extract (25 μg/ml) and of gentamycin (25μg/ml).

The fibroblasts and the keratinocytes were cultured in 96-well plates.At confluence, the culture medium was replaced with suitable culturemedium containing or not containing (control) the test compound or thereference, and then the cells were incubated for 48 hours. The35S-sulfate radioactive label was added (40 μCi final concentration) andthe cells were incubated for a further 24 hours. All the conditions werecarried out 3 times.

The extracellular matrix glycosaminoglycans were extracted with onevolume of chaotropic buffer (50 mM Tris/HCl, 4 M guanidine, 5 mM, EDTA,pH 8.0). The sulfated GAGs were purified by ion exchange chromatography:absorption of the anionic molecules onto Q-Sepharose beads underhigh-stringency conditions, desorption of the molecules which are notvery anionic and molecules which are moderately anionic, with a 6 M ureasolution containing 0.2 mM NaCl, and then washing.

The radioactivity incorporated into the highly cationic molecules thathave remained on the support (predominantly GAGs) was measured by liquidscintillation.

The results are evaluated relative to a control consisting of cellswhich have not been treated with a compound of formula (I).

A positive control (TGFβ at 10 ng/ml) known to stimulate GAG synthesisis introduced into the test carried out on fibroblasts, as a positivereference.

A positive control (CaCl₂ at 1.4 mM) known to stimulate GAG synthesis isintroduced into the test carried out on keratinocytes, as a positivereference.

The results are expressed as percentage variation in glycosaminoglycansynthesis relative to the control.

3 tests were carried out for the tested compound.

The comparisons of the results obtained for a tested compound werecarried out using the Student's test.

The standard deviation of the mean (sem) was calculated according to thefollowing relationship:

sem=standard deviation/(n)^(1/2)

n being the number of tests carried out.

The results are given in the following table:

Mean Treatment on fibroblasts value sem n % p Control (culture medium)2332 7 3-3 100-100 0.01 to 0.05 Positive control (TGFβ) 4062 9 3-3 174<0.001 Compound of  40 μM 8130 28 3 351 <0.001 example 2 120 μM 15318 223 657 <0.001

Mean Treatment on keratinocytes value sem n % p Control (culture medium)4526 4 3-3 100-100  0.01 to 0.05 Positive control (CaCl₂) 5273 3 3-3 1170.001 to 0.01 Compound of 0.37 mM 31999 23 3 707 <0.001 example 2  1.1mM 36795 34 3 813 <0.001

The values measured are given in counts per minute (cpm)

n: number of tests carried outp: confidence intervalsem: standard deviation of the mean

The results obtained show significantly that the compound of example 2(compound 1) is very effective for increasing sulfated GAG synthesis.This activity makes it possible to attribute to this compound abiological activity on the firmness of the skin, and thus to soften thesigns of aging of the skin.

In another experimental plan, the compounds of example 5 (compound 9)and of example 6 (compound 8) were evaluated.

Mean Treatment on fibroblasts value sem n % Control (culture medium)2518 2 2 100 Compound 8 of 0.1 mM 2938 13 2 117 example 6   1 mM 1037134 2 412 Compound 9 of 0.1 mM 10838 9 2 430 example 5   1 mM 23620 21 2938

Mean Treatment on keratinocytes value sem n % Control (culture medium)4526 4 2 100 Compound 8 of 0.1 mM 40552 40 2 316 example 6   1 mM 8545647 2 665 Compound 9 of 0.1 μM 24106 5 2 563 example 5   1 μM 99041 112 2547

The results obtained show significantly that compounds 1, 8 and 91 arehighly effective for increasing sulfated GAG synthesis.

This activity makes it possible to attribute to this compound abiological activity on the firmness of the skin, and thus to soften thesigns of aging on the skin.

EXAMPLE 7

A face care cream of oil-in-water emulsion type is prepared, comprising(% by weight):

Compound of example 2 0.005%  Glyceryl stearate   2% Polysorbate 60(Tween 60 from ICI)   1% Stearic acid 1.4% Triethanolamine 0.7% Carbomer0.4% Liquid fraction of shea butter  12% Perhydrosqualene  12%Antioxidant qs Fragrance, preservative qs Water qs 100%

A similar composition is prepared with the compound of examples 1 or 3to 5.

The composition applied to the face makes it possible to reinforce thefirmness of the skin and thus to soften the signs of aging on the skin.

EXAMPLE 8

An anti-aging gel for the skin is prepared, comprising (% by weight):

Compound of example 2 2% Hydroxypropylcellulose (Klucel H from Hercules)1% Antioxidant qs Fragrance, preservative qs Isopropanol 40%  Water qs100%

A similar composition is prepared with the compound of examples 1 or 3to 5.

The composition applied to the face makes it possible to reinforce thefirmness of the skin and thus to soften the signs of aging on the skin.

What is claimed is:
 1. A compound selected from the group consisting of1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-ol and1-(α,β)-D-xylopyranosyl-4-(4-hydroxy-3-methoxyphenyl)butan-2-one; andthe salts thereof or the solvates thereof.
 2. The compound according toclaim 1 being 1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-ol; and the saltsthereof or the solvates thereof.
 3. The compound according to claim 1being 1-(α,β)-D-xylopyranosyl-4-(4-hydroxy-3-methoxyphenyl)butan-2-one;and the salts thereof or the solvates thereof.
 4. A cosmetic orpharmaceutical composition comprising, in a physiologically acceptablemedium, at least one compound according to claim
 1. 5. The cosmetic orpharmaceutical composition according to claim 4, wherein said compoundis 1-(α,β)-D-xylopyranosyl-4-phenylbutan-2-ol; and the salts thereof orthe solvates thereof.
 6. The cosmetic or pharmaceutical compositionaccording to claim 4, wherein said compound is1-(α,β)-D-xylopyranosyl-4-(4-hydroxy-3-methoxyphenyl)butan-2-one; andthe salts thereof or the solvates thereof.
 7. The composition as claimedin claim 4, in which said compound is present, alone or as a mixture, inan amount of between 0.01% and 10% by weight relative to the totalweight of the composition.
 8. The composition as claimed in claim 7, insaid compound is present, alone or as a mixture, in an amount of between0.1% and 5% by weight.
 9. The composition as claimed in claim 7, inwhich said compound is present, alone or as a mixture, in an amount ofbetween 0.5% and 3% by weight.
 10. The composition as claimed in claim4, in which the physiologically acceptable medium comprises at least onecosmetic adjuvant chosen from water; organic solvents; hydrocarbon-basedoils, silicone oils, fluoro oils, waxes, pigments, fillers, dyes,surfactants, emulsifiers, cosmetic or dermatological active agents,UV-screening agents, film-forming polymers, hydrophilic or lipophilicgelling agents, thickeners, preservatives, fragrances, bactericides,odor absorbers and antioxidants.
 11. The composition as claimed in claim4, in which the physiologically acceptable medium comprises at least onecompound chosen from: desquamating agents; moisturizing agents;depigmenting or propigmenting agents; anti-glycation agents; NO-synthaseinhibitors; agents which stimulate the synthesis of dermal or epidermalmacromolecules and/or prevent degradation thereof; agents whichstimulate fibroblast and/or keratinocyte proliferation or stimulatekeratinocyte differentiation; muscle relaxants and/ordermo-decontracting agents; tensioning agents; anti-pollution agentsand/or free-radical scavengers; agents which act on themicrocirculation; agents which act on the energy metabolism of cells;and mixtures thereof.
 12. The composition as claimed in claim 4, whichis in the form of an anti-aging, composition intended for combating theexternal signs of aging of the skin.
 13. A method for nontherapeuticcosmetic treatment of the skin, comprising the application, to the skin,of a cosmetic composition as defined in claim
 4. 14. A method fornontherapeutic cosmetic treatment of the skin, comprising theapplication, to the skin, of a cosmetic composition as defined in claim5.
 15. A method for nontherapeutic cosmetic treatment of the skin,comprising the application, to the skin, of a cosmetic composition asdefined in claim
 6. 16. The method as claimed in claim 13, wherein thecomposition is applied to mature and/or wrinkled skin.
 17. The method asclaimed in claim 14, wherein the composition is applied to mature and/orwrinkled skin.
 18. The method as claimed in claim 15, wherein thecomposition is applied to mature and/or wrinkled skin.
 19. Thenontherapeutic cosmetic treatment as defined in claim 13, whichcomprises improving the firmness of the skin and/or improving thestructure of the dermal-epidermal junction and/or reinforcing thecohesion between the dermis and the epidermis.
 20. The nontherapeuticcosmetic treatment as defined in claim 14, which comprises improving thefirmness of the skin and/or improving the structure of thedermal-epidermal junction and/or reinforcing the cohesion between thedermis and the epidermis.
 21. The nontherapeutic cosmetic treatment asdefined in claim 15, which comprises improving the firmness of the skinand/or improving the structure of the dermal-epidermal junction and/orreinforcing the cohesion between the dermis and the epidermis.
 22. Thenontherapeutic cosmetic treatment composition as defined in claim 13,which comprises preventing and/or treating the signs of aging on theskin.
 23. The nontherapeutic cosmetic treatment composition as definedin claim 14, which comprises preventing and/or treating the signs ofaging on the skin.
 24. The nontherapeutic cosmetic treatment compositionas defined in claim 15, which comprises preventing and/or treating thesigns of aging on the skin.